Coronavirus vaccines?

The latest issue of Affinity’s Social Issues Bulletin is out now. It is free to download, as are all previous editions. One of the articles, by Dr John Ling, looks at the current state of play with regard to vaccines for coronavirus and discusses the some ethical issues which are rarely mentioned.

(Note: this was written before yesterday’s announcement that the Pfizer / BioNtech vaccine is claimed to be 90% effective and will become available for use as early as next month.)

Coronavirus – where to start? And when to stop? Our news screens are full of it, our lives are subject to it, and the misinformation is troubling. So, if vaccines are the answer, what are the questions? How are they made? How are they tested? Are they medically safe? Are they ethically sound? Are some bioethically dubious? What should we think and do? This year a few of us will be infected by Covid-19, next year all of us will be faced with a Covid-19 vaccine. We need knowledge and understanding. Here goes:

Vaccines – the basics

Vaccinations save millions of lives each year. Vaccines prepare a person’s immune system to recognise and fight particular viral and bacterial infections. If a vaccinated person is subsequently exposed to disease-causing organisms, the body is primed to attack and destroy them, thus preventing the illness. Such a strategy already prevents 2 to 3 million global deaths each year from diseases like diphtheria, tetanus, pertussis, influenza and measles.

Lockdowns are temporary, vaccines are permanent (probably, maybe). Vaccination is widely considered to be one of the long-term answers to controlling SARS-CoV-2, the virus that causes the disease Covid-19. There is currently a concerted world-wide push to make it a vaccine-preventable disease. So, how is vaccine progress made? Typically, scientists take several years to prepare a vaccine before testing it on people. Such early safety trials, known as phase 1 and phase 2, take several years to complete. If all goes well – and it normally does not – then phase 3, the final stage, can begin, comparing thousands of people who receive the vaccine with thousands who are given a placebo. It may take another three years to get these results. Only then – a decade or more after the research was begun – will a vaccine manufacturer build a factory to make the successful product. Then there is the issue of distribution. Getting a vaccination programme to 80% of global coverage generally takes about another 30 years.

Covid-19 vaccine strategies

That protracted procedure is clearly not the plan for Covid-19 vaccines – the world is in a hurry. So the World Health Organization (WHO) has already arranged a strategy, known as the Solidarity Vaccines Trial. Several vaccines will be given at random to one large group of volunteers, while a smaller group will receive the placebo. It has taken nine months to get off the ground, but this trial is due to start in late October with a small study in Latin America.

The US Government has taken a different tack. It has opted for a ‘harmonised approach’. This will allow vaccine makers to run their own trials, but only if they follow certain guidelines and let the National Institutes of Health (NIH) test all of their volunteers in the same way. In exchange for following these rules, the pharmaceutical companies will benefit from using the network of NIH clinical testing sites and they will receive some of the US Government’s promised $10 billion vaccine fund.

As of late October, AstraZeneca, Johnson & Johnson and Moderna have begun trials in this network. Novavax and Sanofi are expected to start their phase 3 studies in the next couple of months. But Pfizer, one of the front-runners, has not joined the network, opting instead to run its own hush-hush trials.

The UK has taken a third way, with up to six possible vaccines currently being developed and tested. Of course, there is the well-known Covid-19 vaccine joint trial being conducted by AstraZeneca and the Oxford Vaccine Group, which began on 20 January. It centres on an already well-studied, and regarded as safe, chimpanzee adenovirus vaccine vector (ChAdOx1), developed at Oxford’s Jenner Institute. This was chosen as the most suitable vaccine technology for a SARS-CoV-2 vaccine as it can generate a strong immune response from just one jab – other potential vaccines may require a booster dose.

A feature of coronaviruses is those familiar club-shaped spikes on their surface coats. This Oxford vaccine contains the genetic sequence of this surface spike protein inside the ChAdOx1 construct. Once vaccinated, the surface spike protein is produced and this readies the patient’s immune system to attack if the virus ever infects the body. If proved effective and granted approval, production of the AstraZeneca Oxford vaccine will be scaled up for distribution across the UK population and also to several other hard-hit countries.

Other UK trials exist. For example, there is the Imperial challenge trial being run by hVivo, a spin-off company from Queen Mary University of London. Already some 2,000 people have signed up to be jabbed and a month later be exposed to the virus. This vaccine works not by delivering a weakened form of Covid-19, but by delivering synthetic strands of the virus’s genetic code. These instruct the patient’s cells to produce the SARS-CoV-2 spike surface protein and the required immune response and hence immunity to the virus.

And the University of Cambridge hopes to start clinical trials soon with its DIOS-CoVax2. This DNA-based strategy uses computer-generated antigen structures that are encoded by vaccinating with synthetic genes. These in turn re-programme the body’s immune system to produce antibodies against the virus. And other UK trials exist, such as that from Synairgen with its experimental drug, SNG001 – an inhaled formulation of interferon-beta-1a, which has known antiviral properties.

In addition, the UK Government has been busy securing doses of vaccines – recently 60 million doses of the inactivated Covid-19 vaccine, VLA2001, were recently purchased from the French company Valneva SE. They will cost £450m for delivery in the second half of 2021 with the option for another 130 million doses for between 2022 and 2025. And other deals have already been signed for 340 million doses of various putative vaccines – we should have enough!

And besides this hunt for effective vaccines there is an on-going UK national clinical trial seeking to identify beneficial treatments for those already suffering from Covid-19. Known as the RECOVERY Trial, it is assessing the beneficial effects of the cheap and low-dose steroid, dexamethasone, plus other drugs, such as azithromycin, tocilizumab, convalescent plasma and REGN-COV2.

There are now more than 200 Covid-19 vaccine candidates under development globally, with about 40 of these in the early human trial phases with 10 in phase 3. And how will the winner(s) be selected? The approval and authorisation of a vaccine will depend on how much protection it provides in a phase 3 trial, in other words, on its efficacy. In June, the US Food and Drug Administration (FDA) set 50% efficacy as the target. But the efficacy of a vaccine in a clinical trial will not necessarily be the same as in a real-world setting. Phase 3 trials have margins of error and the actual efficacy may be higher, or lower.

Furthermore, this current vaccine race has important downsides. For instance, once a particular vaccine has proved sufficiently efficacious and has been selected for mass use, will other vaccine manufacturers drop out of trials, even if, in the long run, their product would have proved to be superior? And because this first wave of vaccines is likely to be reserved for healthcare workers and other high-risk groups, does this imply that such valuable test ‘guinea pigs’, working in infected environments, will not be available and eligible to enter other new clinical trials?

Yet all of this means that by spring or summer 2021, there will probably be several coronavirus vaccines for consumers to choose from. But the selection will be complex. It is hoped, for example, that across all trials, some molecular signature in a vaccinated person’s blood will show they are protected. However, there is no guarantee that such a signature will emerge. And if it does, how long will it persist indicating that the person is still protected? Our current knowledge about the short-term attributes of such vaccines is poor while their long-term traits remain largely unknown. For example, the preservation of vaccine efficacy and the appearance of dangerous side effects are two big unknowns for the foreseeable future.

Vaccine general ethics

From all the candidate vaccines in production and in clinical trials, presumably some will become globally available. Which to opt for? Will only one be offered locally or nationally, or will there be a choice? Will vaccination be mandatory? That is unlikely based on a US survey conducted earlier this year which reported that less than 50% of respondents would commit to getting a coronavirus vaccine whenever it becomes available. That famous entrepreneur, Elon Musk, has already unhelpfully stated that he and his family would not take a coronavirus vaccine even if it became immediately available. ‘I am not at risk, neither are my kids’, he has rather foolishly said.

Of course, such behaviours may change in the real world. But people with vaccine hesitancy and vaccine refusal exist. The refusers are unlikely to be just conspiracy theorists, misinformed sceptics and anti-vaxxers. An October 2020 report in The Lancet noted that 31 million people follow anti-vaccine groups on Facebook and around one in six British people were unlikely to agree to being vaccinated. Maybe that is not so surprising when even hard-nosed scientists fail to agree on most aspects of Covid-19.

There is a palpable public mistrust over so many facets of Covid-19. None of this has been helped by Russia and China apparently, and clandestinely, surging ahead. Safety and transparency have been too often lacking – they are essential. Pharmaceutical companies and their academic partners need to disclose and explain their protocols and results. Concerns about vaccines being too hastily approved, suspicion of the giant biotech corporations’ motives and the increase of vaccine misinformation are combining to erode the public’s trust in how vaccines are approved and used.

A prime example of this need for safety and transparency occurred in the UK with the much-favoured Oxford vaccine, produced by AstraZeneca in collaboration with Oxford University. All was apparently going well until 6 September, when phase 3 trials of the Oxford vaccine were suspended by AstraZeneca in the UK, USA and Brazil after a serious adverse reaction occurred in one of the nearly 30,000 test volunteers. The female patient was rushed to hospital after she displayed symptoms of transverse myelitis (TM) – a rare condition affecting the spinal cord. AstraZeneca stated that there would be a ‘voluntary pause of vaccination across all trials’ as part of ‘a standard review process’. It was reported that by 12 September the trials had resumed, with the exception of those in the USA. However, there was a dearth of information from AstraZeneca. Perhaps this largely unexplained incident will serve as a wake-up call about the need for communication of vaccine testing and its safety and transparency.

No other seriously adverse effects have been reported. However, high fever, body aches, headaches and exhaustion are some of the symptoms participants in Moderna’s and Pfizer’s vaccine trials have suffered post-vaccination. While the symptoms have been uncomfortable, and at times intense, they have typically subsided after a day or less.

Vaccine pro-life ethics

But there is another, and much more troublesome, issue surrounding Covid-19 vaccines. Are some vaccines manufactured from aborted human material? If so, are they ethically acceptable to be used by pro-life people?

Here is the most current newsworthy example. It relates to the so-called AstraZeneca Oxford vaccine again. Scientists at the University of Oxford have engineered a chimpanzee cold virus that contains important fragments of the SARS-CoV-2 virus that causes Covid-19. This chimpanzee cold virus is being grown in human fetal cells. When injected into macaques, this engineered virus acts as a vaccine, triggering an immune response that protects these primates so that they do not develop serious disease. But here is the rub. These ‘human fetal cells’ come from a cell line known as HEK-293. This was derived from the kidneys of a girl aborted in the Netherlands in 1972. HEK-293 cells are commonly described as ‘immortalised epithelial cells’, never as stem cells. The line was cultured by Alex Van der Eb in the early 1970s at his laboratory at the University of Leiden, Holland. The source of the cells was an aborted female fetus of unknown parentage. The name HEK-293 was derived from Human Embryonic Kidney and it was one of Eb’s collaborator’s 293rd experiment.

Does this present a bioethical problem? The aborted girl would by now probably be a 40-year-old mother with her own family. Is the origin of HEK-293 sufficiently time-distant to make little or no difference? Should we benefit from the body parts of a non-consenting human being? Does our lack of direct involvement absolve us? About these things, we will disagree.

Many human fetal cell lines, and HEK-293 in particular, have been obtained mostly from elective abortions that are now not contemporary. They have been used often and widely in medical therapies ranging from the production of anti-psychotic drugs to cancer immunotherapies, from vaccines against rabies and rubella to studies for treatments of Parkinson’s disease, spinal cord injuries and degenerative diseases, such as motor neurone disease (MND).

Covid-19 and President Trump

It was perhaps somewhat fitting that the acerbic leader of the most powerful nation in the world should catch Covid-19 and subsequently inflame a global row about its treatment. On 2 October, President Trump developed worrisome symptoms and tested positive for Covid-19. He was flown to the Walter Reed Army Medical Center in Maryland, where, within 24 hours, he had received an experimental, cutting-edge antibody treatment not available to other Americans. The White House stated that among his other on-going therapies Trump had received ‘a single 8-gram dose’ of ‘an emergency cocktail of anti-coronavirus antibodies’, known only as REGN-COV2. It belongs to a promising new class of antiviral drugs, and is produced by Regeneron Pharmaceuticals of New York State.

The US king of misinformation, fake news and sloppy behaviour regarding Covid-19 had been infected and struck down, right in the midst of a presidential election campaign. Yet Mr Trump said he believed that REGN-COV2 had helped him vanquish his coronavirus infection in record time. But there was more. Here was the most pro-life US President ever, and an outspoken opponent of fetal tissue research, being accused, albeit mostly inaccurately, of taking drugs made with cells from an aborted fetus. He was lambasted by his critics. The UK newspaper Metro declared, ‘Trump faces hypocrisy allegations after it was revealed Regeneron [sic] is made from stem cells originally taken from an embryonic kidney.’ And the MIT Technology Review, more accurately claimed, ‘Trump’s antibody treatment was tested using cells originally derived from an abortion.’ Social media users were harsher. Here is one Twitter message, ‘So it turns out that monoclonal antibodies that Trump is on are from fetal stem cells. So Trump is being treated/saved with dead babies. Republicans? Amy Barrett? Pro-lifers? Anybody?’

Was this true or was it fake news? According to Regeneron, REGN-COV2 is manufactured in cells from Chinese hamster ovaries, so-called ‘CHO’ cells – not in human cells. Nevertheless, the involvement of HEK-293 again arises. But this cell line, originally derived from a human fetus, was being used in another way. According to Regeneron, laboratory tests used to assess the potency of its antibodies employed a standardised supply of cells called HEK-293T, a stable clone of HEK-293, which, over the years, has been transformed from the original cell line, meaning it should no longer be considered as ‘fetal tissue’.

So, while Regeneron did not directly use human fetal cells to make the monoclonal antibody treatment given to Trump, it did use cells derived remotely from that 1972 Dutch abortion to make the targets for its antibodies – the mimics of the spike protein of the SARS-CoV-2 virus. Monoclonal antibodies home in on specific targets. To fight coronavirus, they are engineered precisely to attack the spike protein used by the virus to grapple onto cells. To make sure their antibodies were working correctly, Regeneron needed to employ laboratory facsimiles of this spike protein, and for that, they used the HEK-293T cells.

Can this story be corroborated? An official statement from the conservative, pro-life US-based Charlotte Lozier Institute by David Prentice and Tara Sander Lee gives a lengthy scientific explanation about the Regeneron therapy. Prentice and Lee conclude, ‘The president was not given any medicines to treat COVID-19 that involved the destruction of human life. No human embryonic stem cells or human fetal tissue were used to produce the treatments President Trump received – period. And finally, the anti-viral medicine remdesivir and the anti-inflammatory corticosteroid dexamethasone, also given to the president to treat COVID-19, are chemicals – no cells of any kind were used to produce these medicines.’

Moreover, a spokesperson for Regeneron explained, ‘We did not use human stem cells or human embryonic stem cells in the development of REGN-COV2. We did use the HEK-293T cell line to test our antibodies’ ability to neutralize the SARS-CoV-2 virus.’ In other words, the HEK-239T tool, developed years ago, allowed Regeneron to determine which antibodies that had been developed might be most effective against the virus. These cells were not used to create the antibody cocktail itself, but they were used to test its potency.

Further confirmatory evidence can be found on the Regeneron Pharmaceutical website under its ‘Regeneron Position Statement on Stem Cell Research’. Part of it reads, ‘The stem cells most commonly used at Regeneron are mouse embryonic stem cells and human blood stem cells. Currently, there are limited research efforts employing human-induced pluripotent stem cell lines derived from adult human cells and human embryonic stem cells that are approved for research use by the National Institutes of Health and created solely through in vitro fertilization.’ That is both honest and, in terms of the use of ‘human embryonic stem cells’, disappointing. But it is not a sufficiently bioethical indictment of Regeneron or its REGN-COV2.

How to think and respond

Let us indulge in a little bioethical casuistry. Can someone who considers abortion to be an evil, a grave injustice, use such medical therapies that were developed in a way that involved that injustice? Yes, but with conditions. Such therapies may be considered morally justifiable, but only if their use does not contribute to any future evil acts, and if their current use is occasioned by a grave proportionate reason. In other words, the use of these vaccines must demand no contemporary evil abortions, and their current use must spring from a virtuous reason that is both seriously and urgently required.

However, some people may still be concerned about the morality of using vaccines, or other medicines, developed from cells historically linked to aborted fetuses. Can a citizen of conscience, who is opposed to everyday abortion, use a vaccine to protect herself and her loved ones during this time of pandemic? Yes, but they can also refuse, even if the vaccination is ethically justifiable. However, society also has a right, and indeed, a moral obligation, to protect its citizens from illness and death. Check out Matthew 7:12. Therefore, justice demands that we balance our concerns with the competing interests in our communities. Indeed, those who refuse to be vaccinated because of their moral concerns should also expect to be prohibited from entering public spaces, such as schools, restaurants, shops and airports, where they may unwittingly catch or spread the disease. Nonetheless, no-one should rub raw another’s conscience – so disagreements among Christians and others may persist. It is a classic Romans 14 situation.

In summary, we live in a complex, but not morally-neutral, world where we stand to benefit from the present and past actions of both virtuous and vicious men and women. How can we apply bioethical, even biblical, principles to negotiate these complexities without losing our moral integrity? In the current pandemic, citizens of good conscience may use Covid-19 vaccines derived with the aid, but not as current, active ingredients, of historically-obtained human fetal cell lines. In addition, such men and women should avoid public scandal by first making their opposition to abortion absolutely clear. The upshot of understanding these issues has been an increased global call for unimpeachably bioethical ‘clean’ vaccines. That would be good. People should not be forced to make the choice between being vaccinated against Covid-19 and acting against their consciences.

What are we to do? It would be nice to live ethically pure lives. But we live in the real world that is perforated with evil and sin. We cannot go out and live in this world without interacting and being tainted by things and people we consider immoral or unethical. Our thinking and our actions are often wrong and naïve. When Boots the chemist started selling the morning-after pill, we boycotted its stores. It did little except temporarily salve our consciences. We now creep back to shop there occasionally. Like many disasters, this Covid-19 pandemic is highlighting weaknesses in ourselves, in our worldviews, skill sets and systems. What are we to do? Live dangerously, but in the hands of God.

John Ling

John Ling is a freelance speaker, writer and consultant bioethicist. He is the author of three books on bioethical issues. He regularly updates his personal website.

(This article was originally published in the Affinity Social Issues Bulletin for November 2020. The whole edition can be found at www.affinity.org.uk)